Variability in small airway epithelial gene expression among normal smokers

Zeinab Ammous, Neil R. Hackett, Marcus W. Butler, Tina Raman, Igor Dolgalev, Timothy P. O'Connor, Ben Gary Harvey, Ronald Crystal

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Background: Despite overwhelming data that cigarette smoking causes COPD, only a minority of long-term smokers are affected, strongly suggesting that genetic factors modify susceptibility to this disease. We hypothesized that individual variations exist in the response to cigarette smoking, with variability among smokers in expression levels of protective/susceptibility genes. Methods: Affymetrix arrays and quantitative polymerase chain reaction were used to assess the variability of gene expression in the small airway epithelium obtained by fiberoptic bronchoscopy of 18 normal nonsmokers, 18 normal smokers, and 18 smokers with COPD. Results: We identified 201 probe sets representing 152 smoking-responsive genes that were significantly up-regulated or down-regulated, and assessed the coefficient of variation in expression levels among the study population. Variation was a reproducible property of each gene as assessed by different microarray probe sets and real-time polymerase chain reaction, and was observed in both normal smokers and smokers with COPD. Greater individual variability was found in smokers with COPD than in normal smokers. The majority of these highly variable smoking-responsive genes were in the functional categories of signal transduction, xenobiotic degradation, metabolism, transport, oxidant related, and transcription. A similar pattern of the same highly variable genes was observed in an independent data set. Conclusions: We propose that genetic diversity is likely within this subset of genes, with highly variable individual-to-individual responses of the small airway epithelium to smoking, and that this subset of genes represents putative candidates for assessment of susceptibility/protection from disease in future gene-based epidemiologic studies of smokers' risk for COPD.

Original languageEnglish
Pages (from-to)1344-1353
Number of pages10
JournalChest
Volume133
Issue number6
DOIs
Publication statusPublished - 1 Jan 2008
Externally publishedYes

Fingerprint

Gene Expression
Chronic Obstructive Pulmonary Disease
Smoking
Genes
Disease Susceptibility
Epithelium
Bronchoscopy
Xenobiotics
Oxidants
Real-Time Polymerase Chain Reaction
Epidemiologic Studies
Signal Transduction
Polymerase Chain Reaction
Population

Keywords

  • Cigarette smoking
  • Expression profiling
  • Lung
  • Pulmonary
  • Transcriptome

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

Ammous, Z., Hackett, N. R., Butler, M. W., Raman, T., Dolgalev, I., O'Connor, T. P., ... Crystal, R. (2008). Variability in small airway epithelial gene expression among normal smokers. Chest, 133(6), 1344-1353. https://doi.org/10.1378/chest.07-2245

Variability in small airway epithelial gene expression among normal smokers. / Ammous, Zeinab; Hackett, Neil R.; Butler, Marcus W.; Raman, Tina; Dolgalev, Igor; O'Connor, Timothy P.; Harvey, Ben Gary; Crystal, Ronald.

In: Chest, Vol. 133, No. 6, 01.01.2008, p. 1344-1353.

Research output: Contribution to journalArticle

Ammous, Z, Hackett, NR, Butler, MW, Raman, T, Dolgalev, I, O'Connor, TP, Harvey, BG & Crystal, R 2008, 'Variability in small airway epithelial gene expression among normal smokers', Chest, vol. 133, no. 6, pp. 1344-1353. https://doi.org/10.1378/chest.07-2245
Ammous Z, Hackett NR, Butler MW, Raman T, Dolgalev I, O'Connor TP et al. Variability in small airway epithelial gene expression among normal smokers. Chest. 2008 Jan 1;133(6):1344-1353. https://doi.org/10.1378/chest.07-2245
Ammous, Zeinab ; Hackett, Neil R. ; Butler, Marcus W. ; Raman, Tina ; Dolgalev, Igor ; O'Connor, Timothy P. ; Harvey, Ben Gary ; Crystal, Ronald. / Variability in small airway epithelial gene expression among normal smokers. In: Chest. 2008 ; Vol. 133, No. 6. pp. 1344-1353.
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